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(870) Metabolic Indicators in Donor Hearts Following Conventional and Temperature Controlled Storage

˜The œjournal of heart and lung transplantation/˜The œJournal of heart and lung transplantation(2023)

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Abstract
PurposeDonor hearts are traditionally cooled on ice after procurement. This approach may result in uneven cooling and hypothermic injury. Temperature controlled storage avoids hypothermic damage but may increase metabolism and reduce high energy phosphates. We hypothesized that temperature controlled storage would not result in the depletion of high energy phosphates and cardiac metabolites in human donor hearts.MethodsHuman donor hearts (n=4 per group) not accepted for transplantation were preserved using one of two techniques for six hours each in University of Wisconsin Machine Perfusion Solution: 1) standard cold storage, or 2) maintenance in a temperature-controlled storage device (SherpaPak®, Paragonix, Inc.) at 4-8°C. Left atrial, right ventricular, and left ventricular tissue biopsies were obtained at end-preservation. 1H and 31P nuclear magnetic resonance spectroscopy (NMR) was performed on myocardial tissue extracts to measure lactate, alanine, phosphocreatine (PCr), adenosine triphosphate (ATP) and inorganic phosphate (Pi). High energy phosphate and lactate/alanine ratios were calculated from NMR data. Metabolites were further quantified by liquid chromatography/mass spectroscopy (LC/MS).ResultsLactate/alanine ratio was significantly higher in tissues from the right ventricle in the SherpaPak® group but left ventricular and left atrial lactate/alanine ratios did not differ between groups. Energy metabolite ratios (PCr/Pi, ATP/Pi, and PCr/ATP) were comparable in all groups. Except for the NAD+/NADH ratio in the left atrium and acetyl CoA from the right ventricle, there were no significant differences in metabolite ratios (NAD+/NADH, ATP/ADP), energy charge, or acetyl CoA by group. See Table.ConclusionOur findings suggest that cardiac allograft preservation with temperature controlled hypothermic storage at 4 to 8°C does not lead to depletion of high energy phosphates or other cardiac metabolites compared to conventional near 0°C cold storage. Donor hearts are traditionally cooled on ice after procurement. This approach may result in uneven cooling and hypothermic injury. Temperature controlled storage avoids hypothermic damage but may increase metabolism and reduce high energy phosphates. We hypothesized that temperature controlled storage would not result in the depletion of high energy phosphates and cardiac metabolites in human donor hearts. Human donor hearts (n=4 per group) not accepted for transplantation were preserved using one of two techniques for six hours each in University of Wisconsin Machine Perfusion Solution: 1) standard cold storage, or 2) maintenance in a temperature-controlled storage device (SherpaPak®, Paragonix, Inc.) at 4-8°C. Left atrial, right ventricular, and left ventricular tissue biopsies were obtained at end-preservation. 1H and 31P nuclear magnetic resonance spectroscopy (NMR) was performed on myocardial tissue extracts to measure lactate, alanine, phosphocreatine (PCr), adenosine triphosphate (ATP) and inorganic phosphate (Pi). High energy phosphate and lactate/alanine ratios were calculated from NMR data. Metabolites were further quantified by liquid chromatography/mass spectroscopy (LC/MS). Lactate/alanine ratio was significantly higher in tissues from the right ventricle in the SherpaPak® group but left ventricular and left atrial lactate/alanine ratios did not differ between groups. Energy metabolite ratios (PCr/Pi, ATP/Pi, and PCr/ATP) were comparable in all groups. Except for the NAD+/NADH ratio in the left atrium and acetyl CoA from the right ventricle, there were no significant differences in metabolite ratios (NAD+/NADH, ATP/ADP), energy charge, or acetyl CoA by group. See Table. Our findings suggest that cardiac allograft preservation with temperature controlled hypothermic storage at 4 to 8°C does not lead to depletion of high energy phosphates or other cardiac metabolites compared to conventional near 0°C cold storage.
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